JP6158082B2 - Enhanced penetration and action - Google Patents

Description

  The invention relates in particular to a skin system equipped with a light source to enhance the penetration and / or action of pharmacological and / or cosmetic active ingredients through human and / or animal skin.

  The active ingredient is administered to the human or animal body in various ways. Three well-established routes of administration are via the skin, such as oral, (eg intravenous) injection, topical and transdermal. Oral administration of the active ingredient is often considered the most convenient for the patient. However, often high doses of active ingredient must be administered to achieve the desired effect. This is mainly due to the fact that oral bioavailability is very low due to loss of active ingredient due to, for example, low absorption in the gastrointestinal (GI) tract and first pass effect. Thus, the applied dose must be high in order to achieve the desired effect in terms of action. The generation of these, at least primarily, unnecessarily high concentrations of active ingredients and their metabolites may cause unwanted side effects even if they are not absorbed into the GI tract. The high bioavailability of the active ingredient can reduce its undesirable side effects. With a few minor exceptions (eg, the treatment of diabetes), administration by injection is still primarily focused on treatments performed by medical professionals in hospitals and clinics. Furthermore, administration by injection is not yet well accepted by patients. Many patients feel uncomfortable taking the active ingredient by injection. Transdermal plaster and bandages can also be used for systemic treatment methods. The skin is very effective as a selective penetration barrier. Transdermal refers to the passage of active ingredients from the skin surface under the influence of a concentration gradient into the stratum corneum (SC) and subsequent diffusion through the dermis through the SC and underlying epidermis into the blood circulation. To do. The skin acts as a passive barrier to penetrating molecules, and SC is the percutaneous progress limiting stage while providing maximum penetration resistance. In the treatment of various diseases, a transdermal therapeutic system (TTS) has been introduced to the market. Examples are fentanyl bandages for the treatment of pain, nitroglycerol bandages for the treatment of angina, bandages with estrogen and testosterone for hormone replacement therapy, bandages with nicotine used in nicotine replacement therapy It is. However, the transdermal route of application is limited to a relatively small number of active ingredients that can penetrate the SC. The same applies to dermal application of topical active ingredients. The delivery of low penetration active ingredients through the SC can be at least partially enhanced by the use of penetration enhancers.

  A penetration enhancer is a substance that promotes absorption of the penetrant through the skin by temporarily reducing the impermeability of the skin. Ideally, these materials should be pharmacologically inert, harmless, non-irritating, non-allergenic. Although at least some of the penetration enhancers used meet these requirements, penetration enhancers only work with a relatively small number of active ingredients and therefore cannot generally be used.

  One of the main advantages with a transdermal system is that a slow release can be achieved without an unnecessary high systemic concentration peak following a sudden decrease in systemic concentration. Thus, the transdermal system allows the systemic level of the active ingredient to be a relatively constant level. Moreover, the dose of active ingredient required to achieve a certain level is often very low compared to the dose required for oral route administration.

  W.-R. Lee et al. Have shown that the penetration of three narcotic analgesics can be enhanced 10-35 fold when the skin is pre-treated with radiation having a wavelength of 2940 nm (Lasers Med. Sci. 2007, 22: 271-278). The author conducted an in vitro porcine skin penetration experiment to evaluate the action of pulsed laser light emitted by an erbium: yttrium aluminum garnet (ER: YAG) laser. The skin was treated with either morphine, nalbuphine and buprenorphine following prior treatment with laser. The authors show that transcutaneous delivery was greatly enhanced by removing a portion of the SC with a laser. Therefore, this method is not suitable for portable and user-friendly applications and is likely to require the intervention and monitoring of medical professionals.

  N. Otberg et al. Showed in GMS German Medical Science 2008, 6, 1-14 that water filtered infrared A (wIRA) can act as a penetration enhancer for locally administered substances. Based on a test of 12 testers, the authors suggest irradiation with wIRA as a penetration enhancer for more hydrophilic substances. They also suggest methods that apply to a wider range of substances. However, the authors do not provide a technical solution for user-friendly portable devices. The author uses a large device (hydrosun®) suitable only for non-portable applications.

  However, current transdermal systems and plasters (both referred to herein as skin systems) that are intended to deliver active ingredients into the skin, rather than into the systemic circulation, have several I have a problem. As already mentioned above, they are limited to a relatively small number of active ingredients that can cross the skin barrier. Furthermore, the dose of active ingredient applied to current treatments based on the skin system is often somewhat higher to compensate for the loss of active ingredient during or through the transfer of the active ingredient. Thus, if the applied dose is sufficiently high, the required concentration of the active ingredient at the site of action can often be obtained. Higher doses can then cause unwanted side effects on the skin (eg, skin irritation), in the skin and / or other tissues. In addition, active ingredients that are currently administered topically by use ointments, oils, gels, claims, emulsions, miniemulsions, lotions and other formulation forms, i.e. without dermatology or transdermal bandages / systems, are treated Show high loss when applied to the subject area. There are various reasons for the loss. First, low permeability can cause high loss of active ingredients. In addition, topically administered active ingredients may be quickly wiped off, for example by clothing.

  One object of the present invention is topical / cutaneous and transdermal administration for the administration of more pharmacological and / or cosmetic active ingredients as known in the prior art (both referred to herein as active ingredients). It is to provide a new skin system that allows wider application of the pathway. Another object of the present invention is to provide a user friendly system that is easy to handle and can be used without control by a medical professional. Another object of the present invention is to provide a method for reducing unwanted side effects of existing therapies.

  Surprisingly, inorganic light-emitting diodes (LEDs), organic light-emitting diodes (OLEDs), polymer light-emitting diodes (PLEDs) and organic light-emitting electricity are used to enhance the penetration of a wide range of pharmacological and / or cosmetic active substances or ingredients. It has been found that a skin system with a light source with a thin light source selected from a chemical cell (OLEC or LEC) can be used. Here, the term “skin system” refers to both the movement of active ingredients through the skin, for example into the blood circulation, and the concentration of locally applied active ingredients in the skin. Thus, the term “skin system” has what is known as a transdermal system and dermoplasty (dermoplasty). The term skin system also has any currently known method of treatment in which the active ingredient is administered topically without the use of dermatological or transdermal bandages / systems. The effect of achieving concentration of the active ingredient applied topically can also be used to obtain the desired therapeutic or cosmetic concentration of the active ingredient while reducing the dose of active ingredient on the skin. Thus, the skin system according to the present invention is intended to increase the concentration in the face of action, or to reduce the dose applied to keep the concentration in the face of action at the desired level, or once transdermally. Allows one to open the skin pathway to a very wide range of new active ingredients that have not been used for the application.

  The term “dermal application” as used herein comprises administration and topical transdermal route or dermal application.

  The thin light source used allows the production of very thin devices that are used either for installation or preferably for mobility. Devices such as bandages with a thin light source may be placed directly under the garment on the skin to be treated. The device further shows uniform illumination of the area to be treated. The intensity of the radiation can be precisely adjusted at a lower level compared to stationary equipment. The device may further be flexible and thus allow for optimal radiation of curved areas such as large wrinkles and / or rounds. In addition, the intensity, duration and wavelength of radiation can be easily adjusted with minimal human interaction without the need to consult an expert such as a physician.

  Skin comprising at least one light source and at least one pharmaceutical and / or cosmetic active ingredient used to enhance penetration and / or action of at least one pharmaceutical and / or cosmetic active ingredient About the system.

  The invention also relates to a skin system comprising at least one light source and at least one pharmacological and / or cosmetic active ingredient used to enhance penetration of at least one pharmacological and / or cosmetic active ingredient.

  Preferably, the light source is a thin light source. Particularly preferably, the thin light source comprises at least one light emitting diode (LED). The light emitting diode may be an inorganic LED or an organic LED. In a preferred embodiment, the at least one LED is an organic LED (OLED) and / or a polymer light emitting diode (PLED).

  Preferably, the skin system comprises three, particularly preferably two, very particularly preferably one thin light source.

  Preferably, the light source comprises three, particularly preferably two, very particularly preferably one light emitting diode or organic light emitting device.

  In a particularly preferred embodiment of the invention, the skin system comprises just one thin light source comprising one organic light emitting device, preferably an OLED.

  In a particularly preferred embodiment of the invention, the skin system comprises just one thin light source comprising one organic light emitting device, preferably OLEC.

  The terms active ingredient and pharmacological and / or cosmetic active ingredient are used interchangeably herein unless specifically stated otherwise.

  The skin system can enhance both the penetration of pharmacological and / or cosmetic ingredients and their action. The radiation emitted by the skin system results in an enhanced penetration of pharmacological and / or cosmetic ingredients without disturbing the integrity of the skin, which is important for fulfilling the protective function. Furthermore, further mechanisms for how the skin system enhances penetration are possible, and the present invention is not limited to any mechanism. Drug action is also enhanced through enhanced penetration. This is due, for example, to a higher degree of penetration, resulting in a higher concentration in the tissue and / or deeper penetration into the tissue. Enhancement of drug action may also be based on the synergistic effect between the well-known beneficial effects of red light or infrared radiation on the skin and the beneficial pharmacological and / or cosmetic effects of the active ingredient. In this way, the skin system has an increased concentration of pharmacological and / or cosmetic ingredients in the face of the action of certain areas of the skin and / or through the skin, for example in the systemic circulation or other tissues. Can provide both deeper penetration of pharmaceutical and / or cosmetic ingredients into the skin.

  In order to reduce the side effects of pharmacological and / or cosmetic ingredients, as outlined above, by reducing the dose required to obtain the necessary concentration in terms of action, the skin system can also May be used. In other cases, to increase systemic levels of pharmacological and / or cosmetic ingredients and / or to reduce the dosage required to obtain the required systemic concentration May be used.

  Thus, the skin system according to the present invention may be used to increase the penetration of systemic and / or local active ingredients.

  The skin system may be applied to any pharmacological and / or cosmetic active ingredient, whether or not currently used for transdermal or topical application. Thus, the dermal system can be used to obtain a transdermal or topical route of administration that is available for both hydrophobic and hydrophilic active ingredients not previously considered for transdermal or topical application.

  Preferably, the skin system comprises at least one pharmacological and / or cosmetic active ingredient already known to be administered by transdermal or topical application.

  Indeed, the skin system can be used for a wide range of active ingredients. The active ingredient may be selected from pharmacological active ingredients and / or cosmetic active ingredients including oils from natural sources.

  Preferably, the skin system according to the present invention comprises a Comfrey root plant extract, in particular a symphytum officinale root plant extract (Kytta ointment®, Kytta Balsam®, Kytta plasma (registered). And at least one active ingredient selected from Kytta Lotion (registered trademark).

  For example, further preferred active ingredients for the skin system according to the invention are those which are generally administered topically, for example diclofenac, ketorolac, ketoprofen, ibuprofen, ketofifen, methylphenidate, aceclofenac. ), Capsaicin, heparin, oxybutynine, epinephrine, camper, vipera ammodytes toxin, arnica montana extract, indomethacin, vitamins, preferably vitamins D and vitamin B12, estrogen, testosterone, progesterone, estradiol, ethinyl estradiol, chondoitin polysulfate, etofenamat Flufenamic acid, caffeine, nicotine, nitroglycerol, scopolamine, rotigotine, rasagiline, alprazolam, bisoprolol, estrogen, rivastigmine, clonidine, buprenorphine, fludroxycortide, mistletoe album, Mandarage, apidinum, bufexamac, acemetacin, azapropazone, celecoxib, dexketoprofen, dexketoprofen, diflunisal, etodolac, etoricoxib, fenbufen, fenoprofen, flurubiprofen, flurubiprofen acid , Meloxicam, nabumetone, naproxen, piroxicam, rofecoxib, sulindac, tenoxicam, thiape Opioids such as phenic acid, valdecoxib, trinitroglycerin, fentanyl buprenorphine, salicylic acid and related salicylates; or any drug used as a local anesthetic such as lignocaine, lidocaine and prilocaine, bupicaine, levobupivacaine, Procaine, ropivacaine, tetracaine, benzocaine or amesocaine hydrochloride, fusidic acid, betamethasone and derivatives and / or combinations thereof.

  Examples of natural oils that can be used as active ingredients of the skin system according to the invention are, without limitation, mint oil, eucalyptus oil, oil from rosemary and lavender oil.

  Based on the present disclosure, more active ingredients may now be added to the list without inventiveness.

  As already outlined, the skin and thus also the transdermal system may comprise more than one active ingredient, which are provided interchangeably with each other under storage and use conditions.

  Components commonly used as a base for creams, ointments or gels may be used as dispersion media for active ingredients according to the present invention. These components include water, hydrocarbon oils and waxes, silicone oils, plant, animal or marine fats or oils (eg, more glycerin esters of saturated fatty acids or polyglycolysed glycerides, cocoa Glycerides or glyceride derivatives (such as fats, cacao or the like), high molecular weight polyethylene glycols, polyoxyethylenes, lanolin and derivatives, fatty acids, fatty alcohols or fatty acid esters (eg octanoic acid, caprylic acid triglycerides or the like) ), Lecithin, polyhydric alcohols or esters, wax esters, sterols, phospholipids and the like. Thickeners such as gums and other forms of hydrocolloids may be included. The dispersion medium may comprise more than one base component.

  When the active ingredient is formulated as a cream, the dispersion medium may comprise substantially more oil-based components than water. When the active ingredient is formulated as an ointment, the dispersion medium may comprise substantially more water than the oil-based component. When the active ingredient is dispensed as a gel, the dispersion medium may substantially comprise water.

  Furthermore, the skin system according to the present invention may comprise one or more film-forming materials.

  A method of softening as may be required for a skin system according to the present invention is disclosed in WO 02/00203.

  The skin system according to the invention may further suitably be one or more transdermal penetration enhancers (which may be surfactants, alcohols, esters, glycols or the like or other suitable transdermal penetration enhancers. ), Wetting agents, surfactants (which may be cationic, nonionic, anionic or polymeric), emulsifiers, antioxidants, preservatives, clays, antifoaming agents, spreading agents, emollients, barriers Additional ingredients may be provided, such as a solubilizing agent for the active ingredient and the like.

  The skin system according to the present invention also comprises ethanol, menthol, thymol, eucalyptol, eucalyptus oil, benzyl alcohol, isopropyl alcohol, propylene glycol, methyl ethanol, phenol, cyclodextrin, ethyl oleate, eugenol, glycerin, levomenol, A solvent such as monoethanolamine oleate, myristyl alcohol, octyldodecanol, methyl alcohol, coconut oil or silicone oil may be provided.

  The presence of the solvent in the skin system according to the present invention allows for controlled transdermal administration of the therapeutic agent. The extent and rate at which local and systemic administration of a therapeutic agent from a topically applied composition occurs is related to the depth and degree of penetration of the active ingredient through the skin.

  The skin system according to the present invention may further comprise a sensory receptive agent to improve the sensory receptive properties of the composite. Such agents include almond oil, glycerol, linseed oil, monoethanolamine oleate, grape oil, mace oil, isopropyl myristate, isopropyl palmitate, palm kernel oil, cocoa butter, wool alcohol. Inclusion of a sensory receptive agent may be used, for example, to enhance the feel of the skin system, which may improve patient compliance. In addition, such agents may have a perceived cooling effect that may provide a positive psychological effect, particularly, for example, when applied to inflamed joints.

  The skin system according to the invention further comprises anise oil, citronella oil, clove oil, eucalyptol, eucalyptus oil, eugenol, juniper oil, lemongrass oil, lemon oil, terpene-free lemon oil, melaleuca oil, Even equipped with sensory cues such as neroli oil, nutmeg oil, olive oil, orange oil, terpene-free orange oil, poppy oil, pine oil, rose oil, sage oil, spearmint oil, lavender oil, thyme oil, vanillin Good.

  Inclusion of such cues in the skin system can provide the patient with pleasant perceptual feedback on use, and the patient and / or the person applying the skin system will recognize that the administration has taken place. Allow and support memory of administration. Such factors can improve patient compliance and provide a positive psychological effect.

  The skin system according to the invention may further comprise an insect repellent such as citronella or lemongrass.

  The use of preservatives may be undesirable because it may cause allergic reactions in sensitive patients, and the present invention is advantageous in avoiding or reducing the risk of such allergic reactions. Preservatives that have been associated with allergic reactions include chlorocresol, hydroxybenzoates (paraoxybenzoates), polysorbates, sorbic acid and the like, and these preservatives are many known Contained in topical composites.

  Further details of materials commonly used in skin systems are disclosed, for example, in WO 2007/066148. Matrix materials used in particular for matrix systems are disclosed, for example, in WO 87/00042 and WO 00/02539.

  Furthermore, a synergistic effect between the beneficial effects of red light and / or infrared radiation and pharmacological and / or cosmetic active ingredients can be observed, ie well known with red and / or infrared light. The beneficial action of the produced beneficial radiation and the pharmacological and / or cosmetic active ingredients can produce a non-linear synergistic effect when applied simultaneously. Thereby, the combination treatment includes totally and partially parallel and continuous treatment with light / radiation and the active ingredient, ie the subject to be treated is also pre-treated with either light / radiation Treatment may be followed with an active ingredient and vice versa.

  Preferably, the skin system comprises three, particularly preferably two, very particularly preferably one pharmaceutical and / or cosmetic ingredient.

  In many cases, the boundary between therapeutic and cosmetic applications is ambiguous and depends on the individual situation and the physician's assessment. In many cases, treatment symptoms are associated with cosmetic considerations. For example, treatment or prevention of acne may have both therapeutic and cosmetic ingredients, depending on the extent of the symptoms. The same is true for psoriasis, atopic dermatitis and other diseases and / or symptoms. Many diseases and symptoms are associated with overt implications often manifested, for example, by changes in the visibility of the subject's skin. These cosmetic or aesthetic changes can often at least partially lead to psychological changes that lead to serious illness.

  Some symptoms or illness may have emphasis on cosmetic ingredients, even if the therapeutic component plays a role. Some of these are chosen from the prevention and / or treatment of anti-aging, anti-wrinkles, acne and vitiligo.

  The present invention also relates to the use of a thin light source as a penetration enhancer for pharmacological and / or cosmetic active ingredients as outlined elsewhere herein. Light sources that can preferably be used for this purpose are LEDs, OLEDs, PLEDs and OLECs, particularly preferably OLEDs, PLEDs and OLECs.

  Preferably, the penetration occurs via skin, particularly preferably meaning animal and human skin.

  Thus, the skin system according to the present invention may be

  The term skin system according to the present invention has no concept of photodynamic therapy (PDT). In PDT, an active ingredient that is activated by almost short wavelength radiation is applied to the subject to be treated. The active ingredient is photochemically activated and undergoes a chemical reaction. In many cases, the precursor is pharmacologically and / or cosmetically inactive, but radiation initiates a conversion from the somewhat inactive state to the active state. PDT is mainly used to treat cancer.

  Preferably, the skin system emits red light and / or radiation in the infrared region. Thus, according to the invention, the light source emits red light with maximum emission in the band between 580 and 700 nm and / or infrared radiation with maximum emission in the band between 700 nm and 3 mm. Skin systems are also the subject of the present invention. Particularly preferably, the emitted radiation has its maximum wavelength in the band between 700 and 4000 nm, very particularly preferably in the band between 700 and 1400 nm. In a particularly preferred embodiment of the invention, the skin system emits radiation having a wavelength in the band between 780 nm and 1400 nm (infrared A).

  In another preferred embodiment, the skin system emits infrared radiation visible light in a band between 590 nm and 700 nm in addition to infrared radiation.

  Particularly preferably, the skin system according to the invention emits light and radiation in a band between 590 nm and 1400 nm.

In certain preferred embodiments, the light source may be an IR-OLED. Any emitter known to those skilled in the art, both fluorescent and phosphorescent emitters, may be chosen as the emitter in the emitting layer of the light source of the present invention. Sensitive excitation energy transfer to radioactive lanthanide ions reported by O'Riordan et al. In Thin Solid Films (06), 497, p299 and by Schanze et al. In Synth.Met. (03), 137, p1013 Reported by William et al. In Appl. Phys. Lett. (06), 89, 083506/1, a phosphorescent emitter with a trivalent lanthanide cation (Ln ³⁺ ) chelated with a plastidic ligand for Cyclometallated (pyrenyl-quinolyl) 2Ir (acac) (cyclometallated (pyrenyl-quinolyl) 2Ir (acac)), λmax = 720 nm, Angew. Chem., Int. Ed. (07), 46 , 1109 by Borek et al., Inorg. Chem. (03), 42, 4253 by Rozhkov et al., J. Org. Chem. (05), 70, 4617 by Finikova et al., Dig. Tech. Pap.-oc. Pt porphyri reported by Brooks et al. In Inf. Disp. Int. Symp. (08), 39, 1975 An example is the thione far-red / near-IR triplet emitter reported by Evans et al., J. Fluoresc. (09), 19, 169.

  Any thin light source may be used in the skin system according to the present invention. Desirable thin light sources have a thickness of less than 5 mm, particularly preferably less than 2 mm, very particularly preferably less than 1 mm. Here, the term light source is used to define a light emitting device that does not have any peripheral electronic devices such as batteries, adhesive elements and switches. If the skin system comprises, for example, an OLED, the thickness of the light source is determined by the layered structure of the OLED including, for example, a hole and electron transport / injection layer, a radiating layer, an electrode and a capsule. In a preferred embodiment, the present invention is that the organic light emitting device is selected from an organic light emitting diode (OLED), a polymer light emitting diode (PLED), and an organic light emitting electrochemical cell (OLEC, also referred to as LECs or LEECs). It is related with the skin system characterized by this.

  OLEDs and PLEDs exhibit a typical layered structure, and the number of layers in devices with small molecule organic functional materials is generally less than polymer light emitting devices. The organic functional material used in OLEDs and PLEDs may be selected from any material commonly used by those skilled in the art. OLEDs and PLEDs are, for example, organic semiconductors, organometallic composites, hole transport materials, hole injection materials, hole depletion materials, electron transport materials, electron injection materials, electron depletion materials, exciton depletion materials, host materials, Fluorescent or phosphorescent emitters, dyes are provided. Furthermore, PLEDs and / or OLEDs are provided with electrodes (cathode / anode) and are encapsulated. Typical structures of OLEDs and PLEDs and commonly used materials are disclosed, for example, in WO 2004/058911 for OLEDs and in WO 2008/011953 for PLEDs.

  In addition, OLEC and the materials used therein are also well known to those skilled in the art. In addition to the materials used for OLEDs and / or PLEDs, OLE materials are required for OLEC. In contrast to OLEDs and / or PLEDs, charge transport is caused by mobile ions in OLEC. Accordingly, materials such as ion transfer metal complexes (iTMCs) and / or ionic liquids are used in OLEC. More details about OLEC can be found, for example, in Pei et al., Science, 1995, 269, 1086.

  In general, light sources selected from OLED, PLED and / or OLEC have a flat or somewhat flat layered structure. However, these light source structures may also have a fiber form. Organic light emitting fibers have been published, for example, by Brenndan O'Connor et al. In US 6538375 B1, US 2003/0099858 (Adv. Mater. 2007, 19, 3897-3900).

  The fiber facilitates the preparation of a flexible and preferably plastic or ductile device for treatment of the subject. The wavelength can be easily adjusted and allows uniform radiation of the subject. Furthermore, by using light emitting OLEDs, PLEDs and / or OLEC fibers, the light intensity and wavelength required for a particular treatment can be tailored by multiple factors. The strength is adjusted, for example, by the number of fibers used (ie, the density of the fibers), which are treated or woven and a voltage is applied. The wavelength can also be easily adjusted. A single fiber may comprise a composite emitter having radiation peaks at various wavelengths. The fiber may also have different segments with emitter material having different emission peaks.

  As used herein, the term fiber means a shape having a length that is much greater than the cross-sectional diameter (or width or height for a non-circular cross-section). In one preferred embodiment of the invention, the term fiber means a shape having a ratio of length to diameter, such as 10: 1 or greater. Particularly preferably, the ratio of length to diameter is 100: 1 or more.

  The OLED used here is generally an electronic device comprising the following continuous layers.

Optional first base layer,
・ Anode layer,
-Optional hole injection layer (HIL),
An optional hole transport layer (HTL) and / or electron depletion layer (EBL),
-Radiation layer (EML),
An electron transport layer (ETL) and / or a hole depletion layer (HBL),
-Optional electron injection layer (EIL),
・ Cathode layer,
-Optional second base layer.

  Further, the OLED may include an exciton depletion layer between the emission layer and the electrode.

  A PLED is an OLED with a radioactive polymer in the emissive layer, which is usually deposited from solution. Typical PLED structures are anode / HIL or buffer layer / interlayer / EML / cathode. The intermediate layer has both hole transport and electron depletion properties. More details about PLEDs with interlayers are disclosed in WO 2004/084260 A2.

  As originally reported by Science 1995, 269, 1086 by Pei et al., An organic light emitting electrochemical cell (OLEC) comprises two electrodes and a mixture or blend of electrolyte and glittering species in between. OLEC is similar to OLED in terms of layered structure, but removes the limitations of anode and cathode selection and can have a much thicker layer compared to OLED.

  The light source may comprise any further material that would be generally considered by those skilled in the art to assemble such a light source. These additional materials include, for example, color conversion materials and / or color filters. Thus, the present invention also provides that the light source further absorbs light from the light emitting device and has maximum emission in the band between 580 and 700 nm and / or maximum in the band between 700 nm and 3 mm. The invention relates to a skin system characterized in that it comprises a down-conversion medium that re-emits infrared radiation with radiation.

  When a color converter is used in the skin system according to the invention, any fluorescent and / or phosphorescent material may be used to obtain red light and / or infrared radiation emitted by the skin system.

  In a preferred embodiment, the color converter is preferably together with fluorescent and / or phosphorescent emitting materials that emit light having an emission peak of less than 600 nm, particularly preferably less than 560 nm, very particularly preferably less than 500 nm. used.

  In another preferred embodiment, the color converter is used with fluorescent and / or phosphorescent emissive materials to emit light that is entirely in the band between 590 and 700 nm.

  In another preferred embodiment, the color converter is used with fluorescent and / or phosphorescent emissive materials to emit light and / or radiation that is entirely in the band between 700 nm and 1400 nm.

  In another particularly preferred embodiment, the color converter is used with a fluorescent and / or phosphorescent material to emit light and / or radiation that is entirely in the band between 590 and 1400 nm.

  The light source may also comprise an inorganic material that can be used for color conversion.

  The color converter may be selected from phosphorescent materials that can be used, for example, in cathode ray tubes, fluorescent displays or lamps. In general, phosphorescent materials include yttrium oxide, yttrium tantalite, barium fluoride, cesium fluoride, bismuth germanate, zinc gallate, calcium / magnesium pyrosilicate, calcium / molybdate, calcium / chloro. Vanadate, barium / titanium / pyrophosphate, metal tungstate, phosphor doped with cerium, phosphor doped with bismuth, phosphor doped with lead, sodium iodide doped with thallium, doped Selected from cesium iodides, rare earth doped pyrosilicates, and lanthanide halides.

In a preferred embodiment, the color converter is a phosphor having a narrow emission spectrum, especially for display applications. Such kind of phosphor comprises a rare earth recombination nucleus that exhibits distinct emission lines instead of bands due to radiative transitions in the 4f ⁿ shell, which are well shielded electrically by 5d and 6s electrons. May be selected from the following compounds: Preferably, such types of phosphors have an absorption effect at wavelengths of 380 nm and above and are disclosed in Lyuji Ozawa and Minoru Itoh, Chem. Rev. 2003, 103, 3836 and references therein. For example, Y ₂ O ₃ : Sm, Y ₂ O ₃ : Eu, Y ₂ O ₃ : Dy, Y ₂ O ₃ : Ho may be selected. Further preferred phosphors include, but are not limited to, ZnS: Cu, Al, ZnS: Cu, Au, Al, Y ₂ O ₂ S: Eu, Y ₂ O ₂ S: Eu, Zn ₂ SiO ₄ : Mn, (KF, MgF ₂ ): Mn, (KF, MgF ₂ ): Mn, MgF ₂ : Mn, (Zn, Mg) F ₂ : Mn, Zn ₂ SiO ₄ : Mn, As, Gd ₂ O ₂ S: Tb, Y ₂ O ₂ S: Tb, Y ₃ Al ₅ O ₁₂ : Tb, Y ₃ (Al, Ga) ₅ O ₁₂ : Tb, Y ₂ O ₃ : Eu, InBO ₃ : Tb, InBO ₃ : Eu, Y ₂ SiO ₅ : Tb You may choose from

In another preferred embodiment, the color converter is not limited to, for example, YAG: Ce, ZnS: Ag + (Zn, Cd) S: Cu, (Zn, Cd) S: Ag, (Zn, Cd) S: Cu, (Zn, Cd) S : (Cu, Cl), ZnS: Ag + (Zn, Cd) S: Cu, Y 2 O 2 S: Tb, (Zn, Cd) S: Cu, Cl + (Zn, Cd) S: Ag, Cl, ZnS: Ag + ZnS: Cu (orZnS: Cu, Au) + Y ₂ ) ₂ S: Eu, InBO ₃ : Tb + InBO ₃ : Eu + ZnS: Ag, InBO ₃ : Tb + InBO ₃ : Eu It has a phosphor.

In a further embodiment, the present invention also relates to an up-converting phosphor. A published phosphor of this kind is, for example, a nanophosphor comprising NaYF ₄ : Yb, Ln, where Ln is Er, Ho and Tm as disclosed in WO 2009/046392. Chosen from the group of

  In a preferred embodiment of the invention, the skin system comprises at least one pharmacological and / or cosmetic active ingredient and the at least one thin light source in the same device. The device may be, for example, a bandage, a skin bandage / plaster or a transdermal bandage, although any other device well known to those skilled in the art may be used. In a particularly preferred embodiment, the skin system depicted in FIG. 1a) is a device comprising a backing layer 1, a layer 2 comprising a light source 5 and a power source 3, and possibly a steering unit 4; 3 may be a printed battery. Furthermore, the device comprises a self-adhesive layer 6. Layer 6 is a reservoir comprising an active ingredient dispersed in a polymer matrix, preferably comprising one or more hydrophilic and / or hydrophobic polymers. The device also comprises a protective foil 7 that can be removed when its use is intended. The light source 5 is preferably an OLED, PLED or OLEC as outlined above. Preferably, the matrix layer 6 is transparent.

  In a further preferred embodiment of the invention, the skin system depicted in FIG. 1b) is a device comprising a backing layer 1, a layer 2 comprising a light source 5 and a power source 3, and possibly a steering unit 4. And the power source 3 may be a printed battery. Further, the apparatus includes a polymer layer 8 that is a reservoir containing an active ingredient, a progress-controlling microporous membrane 9, an adhesive layer 10, and a protective foil 7.

  The printed battery may be selected, for example, from “soft battery” by Enfucell Oy of Finland.

  The skin system comprising at least one active ingredient may further comprise an additional penetration enhancer. In principle, any technique for enhancing penetration known to the skilled worker may be used. The present invention also includes ethanol, dimethyl sufoxide, derivatives of n-alkyl-azacycloheptanone (eg, laurocapram, azone), fatty acids and esters of fatty acids (eg, oleic acid, glycerol monooles). The skin system further comprises a chemical penetration enhancer such as glycerol monooleat, lauryllactat, 1,2-propylene glycol. The further penetration enhancer may be mixed with the active ingredient in one layer or may be in another layer, preferably in the same layer.

  In another preferred embodiment, the skin system according to the invention comprises an additional layer between layer 2 and protective foil 7. This additional layer acts as an absorption layer that absorbs radiation at either or both of broadband wavelengths or specific wavelengths. One well-known drawback of infrared radiation is that it can cause skin dryness. Thus, infrared B and C region (IRB and IRC) radiation from the light source may be filtered. In addition, some specific wavelengths in the infrared A (IRA) region may also be undesirable in medical and / or cosmetic applications. Specifically, radiation having a wavelength of 944 nm, 1180 nm and / or 1380 nm may be filtered. A variety of filters are available that can be used for this purpose and are well known to those skilled in the art. One preferred filter that may be used in accordance with the present invention is water. Water absorbs IRB and IRC radiation and 944 nm, 1180 nm and 1380 nm radiation. The thickness of the layer comprising water is preferably less than 5 nm, particularly preferably less than 3 mm, very particularly preferably less than 2 mm. The filter layer may be made of pure water surrounded by polyethylene, for example. In addition, the filter layer can be a hydrogel (eg, polyacrylic acid, a derivative of cellulose such as methylcellulose or carboxymethylcellulose, bentonite, aerosil), a hydrophilic ointment (macrogoles with PEG, ie polyethyleneglycole). Water) such as water with hydrophilic claims (eg with Na-dodecyl sulfate, polysorbate 20, 60, 80, macrogolstearate, cetylstearylalcohol) May be provided with a hydrophilic preparation comprising Water-filtered IR radiation can significantly enhance the penetration of more hydrophilic materials. As shown by N. Otberg et al. In GMS German Medical Science 2008, 6, 1-14, one possible mechanism is stratum corneum hydration. The skin system according to the present invention may also be used to enhance the penetration of heat labile active ingredients. This can be achieved, for example, by pre-treating a subject to be treated first with the device depicted in FIG. 1c) and subsequently administering the active ingredient thereto without further radiating the same area of the subject to be treated. May be implemented.

In yet another preferred embodiment, the skin system according to the invention comprises a phosphorescent material that clearly emits the desired wavelength in the infrared band, in particular the IR-A band. Thus, the skin system comprises an emitter that emits light in the visible portion of the spectrum that is absorbed by the phosphorescent material and re-emitted into the IR-A band by the phosphorescent material. Such kind of down-conversion can be carried out with phosphorescent materials such as Al _x Ga _1-x As or rare earth gallium aluminate (see FIG. 4).

  The skin system according to the invention may also consist of two different units. The first unit preferably comprises a thin light source selected from LEDs, PLEDs, OLEDs and OLECs, particularly preferably selected from PLEDs, OLEDs and OLECs.

  The choice as the light source is given to OLEC. Further choice as a light source is given to OLEDs and PLEDs. The second unit may be any formulation of active ingredient such as an ointment, claim, gel, lipogel, hydrogel, liposome, emulsion, miniemulsion, powder, oil, paste, milk or lotion. The second unit may be conventionally administered to the subject to be treated, in particular human or animal skin. Thereafter, the first unit may be attached to a subject treated with the first unit. Preferably, the second unit is placed in the same area as previously treated with the first unit. The invention therefore also relates to the use of thin light sources, preferably LEDs, OLEDs, PLEDs and OLECs, particularly preferably OLEDs, PLEDs and OLECs, for enhanced penetration of pharmacological and / or cosmetic active ingredients. Treatment in both units may be done in parallel. In addition, it is advantageous to first pre-treat the subject to be treated with a light source and then administer a second unit, ie the dispensed active ingredient. It may also be advantageous to first administer the active ingredient and then attach the thin light source after a certain time. The invention also relates to a method for enhancing the penetration of pharmacological and / or cosmetic active ingredients, preferably by using said at least one light source that emits light and / or infrared radiation in the spectrum of the red region. Active ingredients and light sources are described elsewhere in the present invention.

  A preferred embodiment of the present invention is a skin that is disposed on a device with the at least one light source, and wherein the at least one pharmacological and / or cosmetic active ingredient represents a spatially different entity. About the system.

  The skin system according to the present invention may be any device suitable for the intended use as outlined herein. Preferably, the skin system is such that the device is a flat panel, curved panel, bandage, bandage, blanket, sleeping bag, sleeve, implantable probe, nasogastric tube, chest drain, pad, stent, salve, any kind of It is characterized in that it is selected from clothes, a device that covers at least one tooth in the mouth.

  Furthermore, the invention relates to said skin system, preferably used as an enhancer of penetration of pharmacological and / or cosmetic active ingredients through human and animal skin.

  Indeed, the skin system may be applied outside or inside the subject to be treated, and the subject to be treated is preferably a human or animal subject.

  Treatment outside the subject may be, for example, treatment of skin, wounds, eyes, gums, mucous membranes, tongue, hair, nail bed or nails. The treatment inside the subject may be, for example, treatment of the subject's blood vessels, heart, chest, lungs or other organs. Most applications inside the subject require special equipment. One such example may be a stent fiber according to the present invention.

  In addition to enhanced penetration, the skin system also provides an enhanced effect of pharmacological and / or cosmetic active ingredients as outlined elsewhere in the present invention, and therefore it is also a subject of the present invention. It is. The enhancement of the action by the skin system, in particular by a thin light source, is due to the enhanced penetration of the active ingredient already penetrating, and by the synergistic effect of the light and / or radiation emitted by the skin system and its active ingredient. By promoting the penetration of active ingredients that previously did not penetrate.

  The skin system may be used to treat any pharmacological and / or cosmetic condition. Preferably, the skin system is used for treating pharmacological (including dermatological) and / or cosmetic conditions that may be treated topically (cutaneously), transcutaneously and / or systemically. May be used. Systemic therapy as used herein includes any therapy that makes the active ingredient available systemically, such as injection and oral administration. Systemic circulation of the active ingredient may be necessary to transport the active ingredient in terms of action.

  Any disease and / or cosmetic (aesthetic) condition can be treated with a skin system that enhances penetration and / or action. This is thanks to the disclosure of the present invention that the skin system can facilitate the penetration of active ingredients that were not previously used for skin application.

  The invention therefore also relates to said skin system used for the treatment and / or prevention of diseases and cosmetic conditions. As used herein, the term disease includes any pharmacological and dermatological disease.

  The following list is not very complete and represents merely a representative selection of possible pharmaceutical and / or cosmetic fields of application and active ingredients suitable for use according to the present invention. In fact, a person skilled in the art can add any pharmaceutical and / or cosmetic application and / or active ingredient not mentioned here without difficulty and without inventiveness based on the present invention.

  Preferably, the skin system is an inflammatory disorder and / or symptom, fibromyalgia, pain, pain around shingles (herpes zoster), muscle pain, muscle stiffness, acute and chronic pain (and severe chronic pain) Treatment of several types of neuropathic pain, opioid detoxification, sleep disorders, joint care, acute injury, wound healing, mood disorders, mental disorders, Parkinson's disease, Alzheimer's disease, motion sickness (car sickness, air sickness) , Seasickness, centrifguges, floating dizziness for spinnin), hypertension, hypotension, nicotine addiction, angina, skin aging, anti-wrinkle, acne, comedones, psoriasis, atopic dermatitis, cellulite Or it may be used for the treatment and / or prevention of arthritis.

  The skin system is also used in the field of hormonal therapy to supply hormones through the skin for the application of contraceptives, for the application of anesthetics, for the treatment of problems associated with osteoporosis, for the application of repellents, and / or Or it may be used in the field of sterilization.

  Further choices include acute and chronic pain, muscle pain, joint stiffness, muscle tone and stiffness, mood disorders, menopause, osteoporosis, angina, acute injury, arthritis, nicotine addiction, viral infections, inflammation, tumors, cancer treatment and Given for prevention.

  Further options are given for the treatment and / or prevention of pain, muscle pain, joint pain, joint stiffness, muscle tone and stiffness.

  However, another option is given to the treatment of acne, psoriasis, wrinkles and skin aging, particularly where treatment and / or prevention has primarily cosmetic / aesthetic aspects.

  In order to enhance their penetration, especially those mentioned above, for the treatment and / or prevention of pharmacological diseases and / or cosmetic conditions, a very different class of active ingredients is one of the skin systems according to the invention. It may be used as a part.

  These compounds are compounds for disinfection (eg antifungal agents, anthelmintic active ingredients), anti-inflammatory active ingredients (eg steroids, non-steroidal anti-inflammatory active ingredients, immune selective Anti-inflammatory derivatives, herbs), active ingredients for itching, active agents for the treatment of psoriasis (eg, active ingredients with disulanol, psoralen, tar extract, calcipotriol), retinoids, It may belong to a class selected from active ingredients used for the treatment and / or prevention of acne, skin aging, wrinkling or cellulite.

  For a more comprehensive list of additional medical instructions and / or cosmetic fields of interest, see, for example, Arzneimittelwirkungen, Lehrbuch der Pharmakologie und Toxikologie, Wissenschaftliche Verlagsgesellschaft mbH, Stuttgart, 9. Auflage, 2008, by E. Mutschler et al. L. Brunton et al., Goodman & Gilman's The Pharmacological Basis of Therapeutics, McGraw-Hill Professional, 11 edition, 2005, WO Foye et al., Principles of Medicinal Chemistry, Lippincott Williams & Wilkins, fourth edition, 1995.

  Preferably, the skin system according to the present invention is a transdermal system. Transdermal absorption is a well-recognized means of drug administration and benefits from being a non-invasive and convenient method of treating patients with drugs. Transdermal absorption is a particularly useful means of administration of the active ingredient for patients who find other methods difficult or unpleasant. For example, both young and old people can struggle with active ingredients that are administered orally, and injections can be particularly unpleasant. Children and demented patients can also have difficulty treating drugs due to lack of compliance. Therefore, transdermal administration of the active ingredient is a valuable method of administration, especially for young, elderly or mentally ill patients.

  There are currently three main types of transdermal application systems: membrane control systems (see FIG. 1b)), adhesive diffusion control systems or matrix systems (see FIG. 1a)).

  The membrane control system generally consists of four layers: an impermeable backing layer 1, a polymer layer 8 that serves as a drug reservoir, a progress control microporous membrane 9, an adhesive layer 10, and a protective foil 7. The drug reservoir 8 includes an active ingredient and a liquid additive that facilitates absorption of the drug across the skin. In application to the skin, the active ingredient diffuses through the membrane and then reaches the skin after passing through the adhesive. The release rate of the active ingredient is constant and therefore the release rate must be maintained at a level slightly below the skin saturation limit in order to provide the most efficient method of administration. US 5,683,712 discloses an example of a membrane control system for transdermal administration of a toxicotherapy drug, wherein a microporous membrane is provided to control the release of the drug, inside the membrane The gel containing the is dispersed.

  The adhesive diffusion control system is very similar to the membrane control system, except that there is no progress control microporous membrane. The system consists of an active ingredient reservoir and one or more progress-controlling adhesive layers next to the skin instead of an impermeable plastic barrier. DE 19849823 discloses an example of an adhesive diffusion control system, where the adhesive bandage provides a backing layer, a reservoir containing the active ingredient, and a non-stick area that allows the active ingredient to pass through the skin. And a pressure-sensitive adhesive layer that overlaps the reservoir.

  In the matrix system, the active ingredient reservoir 6 is in direct contact with the skin. Therefore, the progress of diffusion of the active ingredient depends on the progress of skin absorption. The system may comprise an impermeable backing layer 1 attached to an active ingredient reservoir consisting of a hydrophilic or hydrophobic polymer containing dispersed active ingredients. WO 87/00042 describes such a system for transdermal administration of verapamil with a substantially uniform progression retained over a long period of time. Alternatively, the system may include an adhesive layer that serves the dual purpose of backing and both the adhesive and the active ingredient reservoir. An example of such a system is described in WO 00/02539, which relates to a bandage containing a non-steroidal rheumatic therapeutic agent.

  If the skin system represents different units in the two spaces, as explained above, the skin system represents the light source as the first unit and the active ingredient dispensed as the second unit. The first unit may resemble the transdermal salve or system described herein, although the active ingredient reservoir is not directly incorporated (see FIG. 1c)).

  The transdermal system according to the present invention comprises a layer 2 comprising a thin luminescent light source 5, potentially a power source 3 and potentially a steering unit 4, in addition to the components of the percutaneous salve / system described above. (FIGS. 1a) and b)). Thus, the light emitting layer may include a power source that is a preferentially printed battery. The power supply may also be by access to an external power source such as a battery. In simple cases, including transdermal systems and plasters, skin systems may not have a steering unit, and the activation of the light source may be by a switch or another method of connecting the device to a power source. . The steering unit may also be suitable for defining a radiation program that adjusts the wavelength, the time of radiation or the intensity of radiation. The radiation may be, for example, continuous or pulsed.

  The transdermal system according to the present invention may take any suitable form. In one preferred embodiment, the transdermal system may take the form of an adhesive bandage (hereinafter “transdermal bandage”). Prominent brands include Band Aid, Curad, Nexcare, Elastoplast, etc., which are incorporated by reference. For example, the transdermal bandage has a backing layer 1, which may be selected, for example, from a woven fabric, plastic or latex rubber having an adhesive, the adhesive may be selected from an epoxy, It is made from the same compound as the adhesive. A light source, preferably a thin film light source, is then bonded to the backing layer by means of an adhesive, the backing layer having a small opening that allows electrical contact to the light source and then absorbs active ingredients. A pad, such as cotton, is applied to the surface of the light source. The absorbent pad is finally covered with a thin protective plastic sheet.

  In another preferred embodiment, the light source may be integrated into the absorbent pad by using a light source in the form of a fiber instead of cotton, such as a fiber OLED or fiber OLEC.

  Transdermal bandages are applied so that the pad covers the wound and the fabric or plastic sticks to the surrounding skin to hold the dressing in place and prevent dirt from entering the wound.

  Active ingredients as described herein can act in a variety of ways. They may be carried across the skin, for example, and act systemically. It is also beneficial to enhance the penetration of active ingredients that are applied locally and act locally. The present invention also relates to a skin system, characterized in that the skin system is a plaster. The intention of a plaster is here understood to deliver the active ingredient to the skin without making it available systemically. Therefore, dermatological agents are considered to be used for topical administration. Well-known dermatology is provided with lidocaine or diclofenac. The plasters according to the present invention further comprise a thin light source, as described above, and also have the structure and the like depicted in FIGS. 1a) to c).

  The invention also relates to the use of said skin system for the care, protection or amelioration of the general condition of skin and hair.

  For the treatment and / or prevention of skin and hair time and / or light and / or environment-induced aging processes, in particular dry skin, wrinkling and / or pigment disorders, and / or UV radiation to the skin The use of said skin system for the treatment and / or prevention of adverse effects is also a subject of the present invention.

  The more general term skin aging refers to both wrinkling and hyperpigmentation. The signs of aging in human skin due to the effects on the skin due to intrinsic and extrinsic factors are the appearance of wrinkled appearance in addition to the appearance of pigmented spots due to the appearance of wrinkles and fine lines Due to the yellowing of the skin, the stratum corneum and epidermis become thicker and the dermis becomes thinner. Determined.

  Some of these signs are particularly associated with endogenous or physiological aging, which is so-called “normal” aging associated with age, while others are exogenous, so-called aging caused by the environment in general. Specific to aging, such aging is in particular photoaging due to exposure to the sun. Other factors that cause skin aging are air pollution, wounds, infections, traumatic general injury, hypoxia, cigarette smoke, hormonal status, neuropeptides, electromagnetic fields, gravity, lifestyle (eg excessive consumption of alcohol), repetitive Face expression, sleep posture or psychological stress factor.

  Skin changes that occur due to intrinsic aging are the result of genetically programmed sequences that contain endogenous factors. This intrinsic aging particularly causes a decrease in the rate of skin cell regeneration, which essentially reduces the appearance of subcutaneous adipose tissue, the appearance of objective damage such as the appearance of fine lines and small wrinkles, the number of elastic fibers And reflected in histopathological changes such as increased thickness, loss of vertical fibers from the elastic tissue membrane, and the presence of large and irregular fibroblasts in cells of this elastic tissue.

  In contrast, extrinsic aging is a histopathology such as thick wrinkles, objective damage such as the formation of struck skin, excessive accumulation of elastic material in the upper dermis, collagen fiber degeneration, etc. Change.

  There are a variety of biological and molecular mechanisms that can be trusted for skin aging, and the process is currently not fully understood. However, both intrinsic and extrinsic factors of skin aging have been found to share a common mechanism [P. U. Giacomoni et al., Biogerontology 2004, 2, 219-229]. These factors cause skin aging because the expression of cell adhesion molecules causes recruitment and leakage of circulating immune cells, which digest the extracellular matrix (ECM) by secreting collagenase, myeloperoxidase and reactive oxygen species. It triggers a process that leads to the accumulation of inviting skin damage.

  Activation of these cell lysis processes causes random damage to these resident cells, which in turn secrete prostaglandins and leukotrienes. The signaling molecule induces the loss of granules of resident mast cells that release the otacoid histamine and cytokine TNF alpha, and thus the endothelial cells that cover the nearby capillaries that release P-selectin, and E-selectin and ICAM- Activates the synthesis of cell adhesion molecules such as 1. This closes the self-maintained micro-inflammatory cycle, which leads to the accumulation or aging of ECM damage.

  Skin systems according to the present invention comprising anti-aging active ingredients may be used to enhance their penetration. This results in either enhanced effects and / or reduced side effects due to the lower doses required to achieve the same result.

  Furthermore, the use of said skin system for the treatment and / or prevention of uneven skin, preferably wrinkles, fine lines, rough skin, large pore skin, cellulite is also the subject of the present invention. Yet another use for the skin system according to the invention is the treatment and / or prevention of common vitiligo.

  The present invention also provides pigmentation and keratosis actinica for the treatment and / or prevention of premature skin aging, in particular for the treatment and / or prevention of light or aging-induced skin wrinkles. It relates to the use of the skin system according to the invention for the treatment and / or prophylaxis of all diseases associated with normal skin aging or light-induced skin aging.

  The present invention also provides for the treatment and / or prevention of skin diseases associated with defective keratinization related to differentiation and cell proliferation, in particular acne vulgaris, acne comedonica, polymorphic acne. Acne solaris, acne solaris, drug-related acne or professionalis acne (adjuvant acne, nodular acne, congenital acne, age-related acne, side-effect acne, acne solaris other disorders of keratinization for the treatment and / or prevention of acne professionalis, in particular ichthyosis, ichthyosis-like conditions, Darier's disease, keratosis palmoplantaris, leukoplakia, vitiligo Related to defective keratinization for the treatment and / or prevention of leukoplasiform states, skin and mucosal (buccal) eczema (moss), inflammatory and / or immunoallergenic components Have other skin diseases A book for the treatment and / or prevention of all forms of psoriasis, particularly on the skin, mucous membranes and finger and toe nails, and rheumatic psoriasis, and skin atopy, eczema or respiratory atopy, or even gingival thickening It relates to the use of the skin system according to the invention.

The present invention also includes benign or malignant pathological growths of the dermis or epidermis that may be the cause of viruses, common warts, adolescent squamous warts, wart-like epidermoplasia, papillomas of the mouth, Treatment and / or prophylaxis of all Florida papillomatosis florida and pathological proliferations that can be caused by UV radiation, in particular epithelioma baso-cellulare and epithelioma spinocellulare The use of the skin system according to the invention for the invention The invention also relates to a method of treating a human or animal with the skin system according to the invention. The details of the method can be directly transferred from those disclosed within the present invention relating to the skin system and the use of the skin system.

  The present invention also provides that in the use of a thin light source for enhanced penetration of pharmacological and / or cosmetic active ingredients through human and / or animal skin, the thin light source is selected from OLED, PLED and OLEC It relates to the use characterized by that.

  The skin used herein also includes mucous membranes, gums, nails, nail beds, as outlined above.

The present invention also provides
a) a thin light source according to the invention,
b) relates to a set (kit) comprising an individual package of active ingredients or a composition of active ingredients or preparations thereof.

  In addition to the advantages outlined within the present invention, further advantages of the skin system according to the present invention can be summarized as follows.

  A thin light source allows the preparation of thin and portable devices used for outpatient treatment.

  • Treatment with the skin system can be performed at almost any place at any time without the need to seek advice from a medical professional.

  The skin system is easy to use and can be attached directly to the skin under clothing and is therefore very user friendly.

  • Lower radiation intensity required compared to conventional approaches due to direct contact with the subject being treated.

  The device according to the invention is flexible and can therefore be adapted to almost any shape of the subject to be treated.

  -Enhanced penetration of the active ingredient results in a higher pharmacological and / or cosmetic effect of the active ingredient.

  • Due to the enhanced osmotic side effects of the active ingredient, the dose required to achieve the desired systemic or local concentration may be reduced.

  More more hydrophilic active ingredients can be administered by the dermal and / or transdermal route.

  The skin system is considered not to interfere with the complete state of the skin, which is important for fulfilling the protective function.

  It will be appreciated that modifications to the previous embodiments of the invention may be made within the scope of the invention. Each feature shown in this specification may be replaced with an alternative feature serving the same, equivalent, or similar purpose unless otherwise indicated. Thus, unless expressly stated otherwise, each feature disclosed is one example only of a generic series of equivalent or similar features.

  All of the features shown in this specification may be combined in any combination, except combinations where at least some of such features and / or steps are mutually exclusive. In particular, the preferred features of the invention are particularly applicable to all aspects of the invention and may be used in any combination. Similarly, features described in non-essential combinations may be used separately (not in combination).

  It will be appreciated that many of the features of the particularly preferred embodiments described above are inventive in their own right rather than as part of an embodiment of the present invention. Independent protection may be sought for those features in addition to or in lieu of any invention presently claimed.

  The teachings disclosed herein may be extracted from and combined with other disclosed examples.

  Other features of the present invention will become apparent in the following description of the drawings and exemplary embodiments. They are given only for illustration of the invention and are not intended to be limiting.

FIG. 1 depicts a different skin system (a or b) or part of a skin system (c). FIG. 2 is an illustration of the preparation of light emitting devices such as OLEDs and OLECs. FIG. 3 is an electroluminescence spectrum of Dev1 to Dev3 according to Example 3. FIG. 4 shows an excitation spectrum (dotted line) and an emission spectrum (solid line) of the infrared phosphor Phos1.

Example of operation Example 1
Materials The light source of the bandage of the present invention has the following device structure: base layer / anode / buffer layer or hole injection layer / intermediate layer / radiation layer / cathode and capsule layer. An additional down conversion layer may optionally be used on top of the capsule layer to further adjust the emission wavelength.

  Flexible poly (ethylene naphthalate) (PEN) is used as the base layer. ITO is used as the transparent anode and PDEOT (Baytron P AI 4083) is used as the buffer layer or hole injection layer. HIL-012 from Merck KGaA is used as the intermediate layer.

  Various electron emitting materials are used in the present invention. In one example, an emissive layer with a red phosphorescent emitter is used, which consists of a matrix material (PTM-011 by Merck KGaA) and a radioactive metal composite (TER-035 by Merck KGaA). In another example, the light source comprises a blue emitting layer and a down conversion layer. As a blue emitter, a blue polymer by Merck KGaA, SPB-090 is used.

Furthermore, for light sources equipped with organic light emitting electrochemical cells (OLEC), poly (ethylene oxide) (PEO) is used as the ion conducting material and LiCF ₃ SO ₃ as the ion source. PEO having a molecular weight of MW = 5 × 10 ⁶ is purchased from Aldrich, accepted and used. LiCF ₃ SO ₃ (LiTrf) is purchased from Aldrich and accepted and used.

  A down conversion material Phos1, which absorbs blue light and emits infrared light again in rare earth gallium aluminate, is purchased from Phosphor Technology, UK and accepted and used. The excitation (dotted line) and emission spectrum (solid line) of Phos1 are shown in FIG. Phos1 has absorption peaks at 465 nm and 620 nm and emission peaks at 885 nm and 1060 nm.

Example 2
Preparation of Light Emitting Device The preparation of both the light emitting device, OLED and OLEC is shown schematically in FIG.

  1) As shown in FIG. 2, 150 nm ITO is sputtered onto the PEN using a mask. The dimensions of the base layer (PEN) and the radiation region are 3 × 3 cm and 2 × 2 cm, respectively.

  2) PDEOT (Baytron PAI 4083) is deposited as a buffer layer with a thickness of 80 nm on the base layer by spin coating and then heated at 120 ° C. for 10 minutes.

  3) A 20 nm intermediate layer is then deposited on PEDOT by spin coating a HIL012 solution in toluene at a concentration of 5 mg / ml, and the intermediate layer is then heated to 180 ° C. for 60 minutes to remove residual solvent. The

  4) A radiation layer is deposited in the glove box by spin coating. The thicknesses and solutions used for spin coating are listed in Table 1. The equipment is heated to remove residual solvent and the conditions for heat treatment for the various equipment are also listed in Table 1.

  5) A cathode is deposited on the emitting layer by thermal vacuum evaporation. The cathodes for various devices are also listed in Table 1.

6) The device is encapsulated. The encapsulation of the light emitting device is achieved using a UV curable resin, UV resin T-470 / UR7114 (Nagase Chemtex Corporation), and a PEN cap, which is a conductor pad as shown in step 4 of FIG. It is smaller than the base layer to free up. UV resin is first applied to the edge of the pixel, and then a cap is placed thereon.
The device is then exposed to UV light for 30 seconds. All these steps are done in the glove box.

Example 3
Evaluation of DEV1, DEV2, DEV3 The devices Dev1 to DEV3 are analyzed by methods well known to the skilled person. A VIL curve and an electroluminescence spectrum are recorded.

The electroluminescence spectra of Dev1 to Dev3 are shown in FIG. The luminance at 6V can be read from the VIL curve, Dev1 is 900 Cd / m ² , Dev2 is 250 Cd / m ² , Dev3 is 500 Cd / m ² .

Example 4
Preparation of Infrared (IR) Radiation Devices DEV4 to DEV6 An IR device is prepared by using DEV1-3 and a down-converting phosphor Phos1.

  Phos1 is dispersed in a silicone binder. IR devices Dev4-6 are prepared by dip coating of Phos1 dispersion on the radiation surface of devices Dev1-3 of Example 2. The emission spectra of Dev 4-6 are recorded by a spectrometer USB2000 (Ocean Optics), which corresponds to the spectrum shown in FIG.

Example 5
Determination of in vitro skin penetration and skin hydration In vitro techniques that can be used for skin penetration analysis are described in detail in L. Simonsen and A. Fullerton, Skin Pharmacology and Physiology 2007, 20, 230-236 . The technical settings as disclosed by L. Simonsen and A. Fullerton are also used here to confirm the results of the study according to the present invention and to compare with published data. Studies as outlined here are thus carried out by methods well known to those skilled in the art.

A sufficiently thick skin is removed from the back of the pig ear. The subcutaneous tissue is removed and the skin is mounted in an open two-chamber Franz type diffusion cell (diffusion area: 3.14 cm ⁻² ; receiving volume: 10 ml). The temperature of the skin surface is kept at 32 ° C. The receiving phase is a 0.05M isotonic buffered acetic acid solution, pH 4.5, 2-propanol (80: 20%, vol / vol). Experiments are performed under sink conditions.

The test formulation is prepared as a 17-valerate (Fucicort® cream, LEO Pharma) with a cream containing fusidic acid (20 mg / g) and betamethasone (1 mg / g). Both active ingredients are commonly used to treat atopic dermatitis (AD). A test formulation (4 mg / cm ² ) is applied to the stratum corneum (SC) surface of the skin. The treatment is applied again at 3, 21, 27, 45, 51h, which simulates the patient's actual dosing schedule. At the appropriate times (3, 21, 27, 45, 51, 70 h), a certain amount of receptive phase is recovered and replaced by the thermosted fluid. Samples are kept at 4 ° C. for up to two days until high performance liquid chromatography (HPLC) analysis. All penetration experiments are performed in 6 replicates. The results of experiments performed by Simonsen et al. Can be reproduced within the statistical variance.

The same experiment as described above is performed. However, the skin is irradiated for 2 h after each application of the cream in the device Dev1 of Example 2. The device is placed directly on the SC. If the cream is applied or reapplied, then the light emitting device is placed on the SC after 5 minutes . After irradiating the skin for 1 h, the radiation source is removed from the skin. Again, recipient samples are taken and analyzed by HPLC at the time intervals given above. The penetration is significantly improved (p <0.005) for both fusidic acid and betamethasone. Compared to the control experiment, the penetration of fusidic acid is enhanced by 16% and that of betamethasone is enhanced by 14%.

The same experiment as described above is performed. Again, the skin is irradiated for 2 h after each application of the cream, but the devices Dev4-6 of Example 4 operate in three separate ways, one for each device. The device is placed directly on the SC. If the cream is applied or reapplied, then the light emitting device is placed on the SC after 5 minutes . After irradiating the skin for 1 h, the radiation source is removed from the skin. Again, recipient samples are taken and analyzed by HPLC at the time intervals given above. The penetration is significantly improved (p <0.005) for both fusidic acid and betamethasone. Compared to control experiments, in all three IR devices (Dev 4-6), the penetration of fusidic acid is enhanced by more than 29% and that of betamethasone is enhanced by more than 27%.

  The same experiment as described above is performed. However, the skin is irradiated at specific time intervals throughout the experiment with the device Dev5 of Example 4. The device is placed directly on the SC. The device is placed 5 minutes after application of the cream and the skin is irradiated for 30 minutes. Thereafter, the light emitting device is removed from the SC. Again, a sample of the recipient is taken and analyzed by HPLC. Despite the short irradiation time, skin penetration is significantly improved (p <0.005) for both fusidic acid and betamethasone. Compared to the control experiment, the penetration of fusidic acid is enhanced by 24% and that of betamethasone is enhanced by 20%.

Furthermore, epidermal hydration can be determined by corneometry. As explained above, the skin behind the pig ear is attached to an open two-chamber Franz-type diffusion cell. The experiment was performed according to methods well known to those skilled in the art, but without applying any cream, as described above. Assessment of skin moisture is done with a corneometer, whereby volume measurements through the SC are used. Corneometric measurements are made before and immediately after irradiation. Epidermal hydration is measured after irradiation of the SC with the apparatus Dev5 of Example 4 for 30 minutes. All experiments are performed in triplicate. Hydration of irradiated skin is improved by 22% (p <0.005).
Hereinafter, the invention described in the scope of claims of the present application will be appended.
[1] A skin system comprising at least one light source and at least one pharmacological and / or cosmetic active ingredient used to enhance penetration and / or action of at least one pharmacological and / or cosmetic active ingredient Wherein the at least one light source is a thin light source comprising at least one inorganic light emitting diode (LED) and / or at least one organic light emitting device.
[2] The light source emits red light with maximum emission in the band between 580 and 700 nm and / or infrared radiation with maximum emission in the band between 700 nm and 3 mm [1] ] The skin system as described in.
[3] The skin according to [1] or [2], wherein the organic light emitting device is selected from an organic light emitting diode (OLED), a polymer light emitting diode (PLED), and an organic light emitting electrochemical cell (OLEC). system.
[4] The light source further absorbs light from the light emitting device and red light having maximum emission in a band between 580 and 700 nm and / or red having maximum emission in a band between 700 nm and 3 mm. The skin system according to one or more of [1] to [3], further comprising a down conversion medium that emits external radiation again.
[5] One or more of [1] to [4], wherein both the at least one light source and the at least one pharmacological and / or cosmetic active ingredient are incorporated in the same device. Skin system.
[6] The apparatus according to any one of [1] to [4], wherein the at least one light source is disposed on a device, and the at least one pharmacological and / or cosmetic active ingredient represents a spatially different entity. A skin system according to one or more.
[7] The device is a flat panel, curved panel, bandage, bandage, blanket, sleeping bag, sleeve, implantable probe, nasogastric tube, chest drain, pad, stent, salve, all kinds of clothes, in the mouth The skin system according to [5] and [6], characterized in that it is selected from devices that cover at least one tooth.
[8] The skin system according to one or more of [1] to [7] for use as an enhancer of penetration of pharmacological and / or cosmetic active ingredients through human and animal skin.
[9] The skin system according to one or more of [1] to [8], for use as an enhancer of the action of a pharmaceutical and / or cosmetic active ingredient.
[10] Treatment of acute and chronic pain, muscle pain, joint stiffness, muscle tone and stiffness, mood disorders, menopause, osteoporosis, angina, acute injury, arthritis, nicotine addiction, viral infection, inflammation, tumor and cancer and / or Or the skin system as described in one or more of [1] thru | or [9] for prevention.
[11] The skin system according to one or more of [1] to [10], wherein the skin system is a transdermal system.
[12] The skin system according to one or more of [1] to [10], wherein the skin system is a dermatological agent.
[13] Use of a skin system according to one or more of [1] to [12] for the care, protection or improvement of a general condition of skin or hair.
[14] For the treatment and / or prevention of skin or hair time and / or light and / or environment-induced aging processes, in particular dry skin and wrinkling and / or pigment disorders and / or to the skin Use of [13] for treatment and / or prevention of adverse effects of UV rays.
[15] Use according to [13] or [14] for the treatment and / or prevention of uneven skin, preferably wrinkles, fine lines, rough skin, large pore skin, cellulite.
[16] Treatment of pigmentation and keratinosis actinica for the treatment and / or prevention of premature skin aging, in particular for the treatment and / or prevention of wrinkles induced by light or aging of the skin [13] to [15] for the treatment and / or prevention of all diseases associated with normal skin aging or skin light-induced aging for and / or prevention Use of.
[17] Acne vulgaris, acne comedonica, polymorphic acne, acne, especially for the treatment and / or prevention of skin diseases associated with defective keratinization with differentiation and cell proliferation Acne professionalis, acne professionalis, acne solaris, acne solaris, drug-related acne or acne professionalis ) Other disorders of keratinization for the treatment and / or prevention of keratosis, especially ichthyosis, ichthyosis-like conditions, Darier's disease, keratosis palmoplantaris, leukoplakia, leukoplakia-like Related to defective keratinization for the treatment and / or prevention of leukoplasiform states, skin and mucosal (buccal) eczema (moss), with inflammatory and / or immunoallergenic components Other skin diseases, For the treatment and / or prevention of all forms of psoriasis on the skin, mucous membranes and fingernails and toenails, and rheumatic psoriasis, and skin atopy, eczema or respiratory atopy, or even gingival thickening [13] Or the use according to one or more of [16].
[18] Benign or malignant morbid growths of the dermis or epidermis that may be the cause of the virus, common warts, adolescent flat warts, wart-like epidermoplasia, papilloma of the mouth, Florida papillae For the treatment and / or prevention of all papillomatosis florida and pathological growths that can be caused by UV radiation, in particular epithelioma baso-cellulare and epithelioma spinocellulare [13] to [17].
[19] A method for treating a human or an animal with the skin system according to one or more of [1] to [12].
[20] In the use of a thin light source for enhanced penetration of pharmacological and / or cosmetic active ingredients through human and / or animal skin, said thin light source is selected from OLED, PLED and OLEC Features use.

WO 02/00203 WO 2007/066148 WO 87/00042 WO 00/02539 WO 2004/058911 WO 2008/011953 US 6538375 B1 US 2003/0099858 WO 2004/084260 A2 WO 2009/046392 US 5,683,712 DE 19849823 WO 87/00042 WO 00/02539

Lasers Med. Sci. 2007, 22: 271-278 GMS German Medical Science 2008, 6, 1-14 Thin Solid Films (06), 497, p299 Synth.Met. (03), 137, p1013 Appl.Phys.Lett. (06), 89, 083506/1 Angew.Chem., Int.Ed. (07), 46, 1109 Inorg.Chem. (03), 42, 4253 J. Org. Chem. (05), 70, 4617 Dig.Tech.Pap.- oc.Inf.Disp.Int.Symp. (08), 39, 1975 J. Fluoresc. (09), 19, 169 Science, 1995, 269, 1086 Adv. Mater. 2007, 19, 3897-3900 Science 1995, 269, 1086 Chem. Rev. 2003, 103, 3836 GMS German Medical Science 2008, 6, 1-14 Arzneimittelwirkungen, Lehrbuch der Pharmakologie und Toxikologie, Wissenschaftliche Verlagsgesellschaft mbH, Stuttgart, 9. Auflage, 2008 Goodman & Gilman ’s The Pharmacological Basis of Therapeutics, McGraw-Hill Professional, 11 edition, 2005 Principles of Medicinal Chemistry, Lippincott Williams & Wilkins, fourth edition, 1995 P. U. Giacomoni et al., Biogerontology 2004, 2, 219-229 L. Simonsen and A. Fullerton, Skin Pharmacology and Physiology 2007, 20, 230-236

Claims (15)

Photodynamic therapy (PDT) used to enhance penetration of said at least one pharmacological and / or cosmetic active ingredient comprising at least one light source and at least one pharmacological and / or cosmetic active ingredient in skin systems except), at least one of said light source is a thin light source comprises a single organic light emitting device even without low, infrared radiation having a radiation maximum in the zone between the light source is 700nm and 3mm A skin system characterized by emitting.   The skin system according to claim 1, wherein the organic light emitting device is selected from an organic light emitting diode (OLED), a polymer light emitting diode (PLED) and an organic light emitting electrochemical cell (OLEC). Wherein the light source further claims absorbs light from the organic light emitting device, characterized in that it comprises a re-emit down conversion medium infrared radiation having a radiation maximum in the band between 7 nm and 3mm The skin system according to 1 or 2.   4. A skin system according to any one of the preceding claims, wherein both the at least one light source and the at least one pharmacological and / or cosmetic active ingredient are incorporated in the same device.   4. The apparatus according to claim 1, wherein the at least one light source is arranged on a device, and the at least one pharmacological and / or cosmetic active ingredient represents a spatially different entity. The described skin system.   The device is a flat panel, curved panel, bandage, bandage, sleeping bag, sleeve, implantable probe, nasogastric tube, chest drain, pad, stent, salve, all kinds of clothes, at least one of the mouth 6. Skin system according to claim 4 or 5, characterized in that it is selected from devices covering one tooth.   7. A skin system according to any one of the preceding claims for use as an enhancer of penetration of pharmacological and / or cosmetic active ingredients through human and animal skin.   The skin system according to any one of claims 1 to 7, for use as a potentiator of the action of pharmacological and / or cosmetic active ingredients.   Treatment and / or prevention of acute and chronic pain, muscle pain, joint stiffness, muscle tension and stiffness, mood disorders, menopause, osteoporosis, angina, acute injury, arthritis, nicotine addiction, viral infections, inflammation, tumors and cancer A skin system according to any one of claims 1 to 8.   The skin system according to any one of claims 1 to 9, wherein the skin system is a transdermal system.   10. The skin system according to any one of claims 1 to 9, wherein the skin system is a dermatological agent. A cosmetic use of a skin system according to any one of the 請 Motomeko 1 to 8, wherein the at least one active ingredient is a cosmetic active ingredients, cosmetic use of a skin system. Cosmetic use according to claim 12, for the improvement and / or prevention of skin or hair time and / or light and / or environment induced aging processes. The cosmetic use according to claim 12 or 13, for the improvement and / or prevention of uneven skin. Cosmetic use according to claim 14, for the improvement and / or prevention of wrinkles, fine lines, rough skin, large pore skin, cellulite.

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